Dual-Responsive Carbon Dots for Tumor Extracellular Microenvironment Triggered Targeting and Enhanced Anticancer Drug Delivery

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• 作者：Tao Feng ; Xiangzhao Ai ; Huimin Ong ; Yanli Zhao
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2016
• 出版时间：July 27, 2016
• 年：2016
• 卷：8
• 期：29
• 页码：18732-18740
• 全文大小：517K
• 年卷期：0
• ISSN：1944-8252

文摘

In this work, pH/redox dual-responsive carbon dots (CDs-RGD-Pt(IV)-PEG) were fabricated for tumor extracellular microenvironment triggered targeting and enhanced anticancer drug delivery. The system consists of fluorescent carbon dots as imaging-guided drug nanocarriers, cisplatin(IV) as prodrug, and RGD peptide as active targeting ligand, which is covered by monomethoxypolyethylene glycol (mPEG) through tumor extracellular pH (6.5–6.8) responsive benzoic-imine bond. The drug nanocarriers could be tracked by multicolor fluorescence of carbon dots. After the hydrolysis of benzoic-imine bond at the tumor extracellular pH to expose the inner targeting RGD peptide, the drug nanocarriers showed effective uptake by cancer cells through RGD-integrin α_vβ₃ (ligand–receptor) interaction. Upon the internalization, the loaded cisplatin(IV) prodrug was reduced to cytotoxic cisplatin in reductive cytosol of cancer cells to exhibit therapeutic effects. Confocal imaging, flow cytometry, and cell viability assays using CDs-RGD-Pt(IV)-PEG were performed to reveal the enhanced uptake and better therapeutic efficiency to cancer cells with high integrin α_vβ₃ expression at tumor extracellular pH than that in physiological condition. The developed CDs-RGD-Pt(IV)-PEG offers a new strategy to provide safe and effective therapeutic agents based on carbon dots for promising cancer therapy.